The major focus of our research program is to understand how cholesterol metabolism is regulated in higher animals. This is a significant goal since large variations can occur in both dietary intake and metabolic demand for this essential cellular metabolite. The regulation of cholesterol metabolism is achieved through feedback regulation of the expression of key proteins involved in its cellular uptake and biosynthesis. A major site for regulating cholesterol uptake and biosynthesis is at the level of transcription for genes that encode important proteins of both processes. The experiments will focus on special aspects of the activity and regulation of the SREBP proteins . These studies will involve 1) examing the potential interaction between SREBP-1 and-2, 2) monitor the time course of the sterol regulated processing of SREBP-1 and -2 from the ER membrane, and 3) evaluate whether the protein that regulates SREBP cleavage in the ER called SCAP co-localizes with either or both SREBP in the ER membrane and determine whether the proximity of SCAP to each SREBP changes during the process of sterol mediated regulation of its processing.